omeprazole, Prilosec
Regulation of aryl hydrocarbon receptor signal transduction by protein tyrosine kinases.

Backlund M, Ingelman-Sundberg M.

Division of Molecular Toxicology, Institute of Environmental Medicine, Karolinska Institutet, SE-171 77, Stockholm, Sweden. maria.backlund imm.ki.se

The involvement of protein tyrosine kinases (PTKs) in aryl hydrocarbon receptor (AhR)-mediated signalling by omeprazole and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) was investigated in hepatoma cells. Both omeprazole- and TCDD-dependent AhR signalling was attenuated by inhibition of c-src kinase, either by using pyrazolopyrimidine 4-amino-5-(4-methylphenyl)-7-(t-butyl)pyrazolo[3,4 ]pyrimidine (PP1) and 4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine (PP2) inhibitors or by expression of dominant-negative c-src. These results indicate that the overall AhR function is modulated by c-src kinase activity. In contrast, a selective inhibition of omeprazole-mediated AhR signalling was revealed by tyrosine kinase inhibitors, tyrphostins AG17 and AG879. Furthermore, omeprazole-dependent AhR activation was abolished by mutation of Tyr320 to Phe, suggesting that this residue is a putative phosphorylation site. TCDD-dependent AhR signalling was neither affected by tyrphostins nor by this mutation. Our results are consistent with activation of the AhR by omeprazole in a ligand-independent manner, via a signal transduction pathway that involves protein tyrosine kinases, and are different from the mechanism exerted by high-affinity ligands. Copyright 2004 Elsevier Inc.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15451023&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Effects of leminoprazole, omeprazole and sucralfate on indomethacin-induced delayed healing of kissing gastric ulcers in rats.

Tsukimi Y, Nozue C, Okabe S.

Department of Applied Pharmacology, Kyoto Pharmaceutical University, Japan.

We have examined whether or not repeated treatment with indomethacin delays the healing of kissing gastric ulcers induced in rats. The effects of leminoprazole, omeprazole and sucralfate on any delay in ulcer healing caused by indomethacin were also determined in relation to myeloperoxidase activity. Kissing gastric ulcers were induced by luminal application of an acetic acid solution. Indomethacin significantly delayed ulcer healing in a dose-dependent manner. Leminoprazole and omeprazole decreased the size and depth of ulcers, the healing of which was delayed by indomethacin, while sucralfate only decreased the ulcer depth. Histological studies showed that indomethacin inhibited tissue contraction and regeneration of the ulcerated mucosa. Leminoprazole and omeprazole prevented the inhibition of these parameters. The myeloperoxidase (MPO) activity of the ulcer portion in animals treated with indomethacin was markedly higher than in the control group. Both leminoprazole and omeprazole, but not sucralfate, significantly reduced MPO activity in contrast to the control value (in the presence of indomethacin). There was a significant relationship between the ulcerated area and myeloperoxidase activity. These results suggested that: (i) leminoprazole and omeprazole prevent the indomethacin-induced delay in ulcer healing by promoting tissue contraction and regeneration of the ulcerated mucosa; (ii) sucralfate prevents the indomethacin-induced delay in ulcer healing via the promotion of the formation of granulation tissue; and (iii) MPO activity will be useful to biochemically ensure the healing state of ulcers.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8713699&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Cost-effectiveness of Helicobacter pylori eradication therapy in duodenal ulcer disease.

Jonsson B.

Stockholm School of Economics, Sweden.

A model analysis applied to Helicobacter pylori eradication found that, following successful healing with omeprazole and H. pylori eradication, virtually all patients were cured and experienced no relapse during the next 5 years. In contrast, almost all of the patients receiving episodic therapy relapsed and, during maintenance therapy with H2-receptor antagonists, most experienced at least one relapse. Although H. pylori eradication initially resulted in higher costs than the alternative therapies, it reduced the risk of recurrence and, for most patients, no future costs were incurred. Even with a worst case scenario, such as an H. pylori eradication rate of only 50%, the H. pylori eradication therapy had a pay-off period of less than 1.3 years compared with maintenance treatment and 3 years compared with episodic treatment. A preliminary analysis also compared the cost-effectiveness of three different H. pylori eradication therapies: omeprazole plus one or two antibiotics, ranitidine plus two antibiotics, and ranitidine plus bismuth triple therapy. The highest eradication rates (in excess of 90%) were achieved using 1-week regimens including omeprazole in combination with either clarithromycin or amoxycillin and a nitroimidazole. These regimens were also shown to be the most cost-effective. As the difference in costs between the therapies is small compared with the savings that can be achieved by successful H. pylori eradication, it is logical that the eradication strategy with the highest eradication rate is the most cost-effective. The model analysis concludes that H. pylori eradication in patients with duodenal ulcer disease is cost-effective in comparison to episodic therapy with omeprazole or maintenance therapy with ranitidine.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8722390&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Suppression of Helicobacter pylori colonization with omeprazole.

Fukuda Y.

Internal Medicine 4, Hyogo College of Medicine, Japan.

The efficacy of omeprazole, 20 mg once daily, in suppressing Helicobacter pylori colonization was studied in 33 patients with peptic ulcers. Omeprazole treatment produced a significant fall in the number of H. pylori colony-forming units in the antrum. This finding, together with the results of a meta-analysis of clinical trials of H. pylori eradication therapy, suggests that combinations of omeprazole and antibiotics may be useful as eradication therapy in patients with peptic ulcer disease and H. pylori infection.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8722408&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Development of an intravenously injectable chemically stable aqueous omeprazole formulation using nanosuspension technology.

Moschwitzer J, Achleitner G, Pomper H, Muller RH.

Department of Pharmaceutical Technology, Biotechnology and Quality Management, Free University of Berlin, Berlin, Germany.

Omeprazole is a proton pump inhibitor, which is used for the treatment of peptic ulcers, reflux esophagitis and Zollinger-Ellison syndrome. It is a poorly soluble, chemically labile drug with a high degradation rate in aqueous media. The aim of this study was to show the feasibility of omeprazole stabilization using the DissoCubes technology and to find optimal production parameters for a stable, highly concentrated omeprazole nanosuspension. The high performance liquid chromatography analysis has proved the predominance of the nanosuspension produced by high pressure homogenization in comparison to an aqueous solution. Even 1 month after production no discoloration or drug loss was recognizable when the nanosuspension was produced at 0 degree C. As a result it can be stated that the production of nanosuspensions by high pressure homogenization is suitable for preventing degradation of labile drugs.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15451536&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Gastrin does not stimulate growth of the rat pancreas.

Chen D, Nylander AG, Norlen P, Hakanson R.

Dept. of Pharmacology, University of Lund, Sweden.

BACKGROUND: Gastrin is thought to stimulate growth of the pancreas via gastrin/cholecystokinin (CCK)-B-type receptors. The aim of the present study was to examine the trophic response of the pancreas to exogenous gastrin or to hypergastrinemia of endogenous origin and to hypogastrinemia with or without concomitant hyperCCKemia. METHODS: Hypergastrinemia was induced in male Sprague-Dawley rats by continuous infusion of human Leu15-gastrin-17 (5 nmol/kg/h, subcutaneously), by removal of the acid-producing part of the stomach (fundectomy), or by treatment with omeprazole (400 mumol/ kg/day, orally). Hypogastrinemia was induced by antrectomy or by gastrectomy. HyperCCKemia was induced by pancreaticobiliary diversion (PBD). The rats were killed 10 days or 8 weeks after the operations or treatments. The concentrations of circulating gastrin and CCK were measured by radioimmunoassay. The pancreatic weight and DNA content were determined. RESULTS: Gastrin infusion, omeprazole treatment, and fundectomy greatly increased the serum gastrin concentration. The resulting levels were very similar in the three groups and probably represent the maximum attainable physiologic serum gastrin concentration. Whereas gastrin infusion or omeprazole treatment (hypergastrinemia) and antrectomy (hypogastrinemia) were without effect on the weight and DNA content of the pancreas, gastrectomy (hypogastrinemia) and fundectomy (hypergastrinemia) increased the weight and DNA content. PBD (hyperCCKemia) greatly increased the weight and DNA content of the pancreas. PBD plus fundectomy, PBD plus gastrectomy, PBD plus antrectomy, and PBD plus omeprazole increased the weight and DNA content of the pancreas, as did PBD alone. CONCLUSION: CCK is a physiologically important trophic stimulus for the rat pancreas, but gastrin is not. The increase in pancreatic weight and DNA content after fundectomy and gastrectomy cannot be explained by means of either gastrin or CCK.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8726311&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
One-week triple therapy with omeprazole, amoxycillin and either clarithromycin or metronidazole for cure of Helicobacter pylori infection.

Labenz J, Stolte M, Peitz U, Tillenburg B, Becker T, Borsch G.

Department of Internal Medicine and Gastroenterology, Elisabeth Hospital, Essen, Germany.

AIM: The present study was designed to evaluate the efficacy and tolerability of 1-week triple therapy regimens for Helicobacter pylori. METHODS: In two consecutive series, 120 patients with proven H. pylori infection and peptic ulcer disease or functional dyspepsia were treated with either omeprazole 20 mg b.d., amoxycillin 1 g b.d. and clarithromycin 250 mg b.d. (OAC; n = 60) or with omeprazole 20 mg b.d., amoxycillin 1 g b.d. and metronidazole 400 mg b.d. over 1 week (OAM; n = 60). H. pylori infection was assessed by rapid urease test, culture and histology before and 4 weeks after cessation of the eradication therapy. RESULTS: H. pylori eradication succeeded in 53 out of 60 patients by omeprazole-amoxycillin-clarithromycin (OAC) (88%; 95% CI 77-95%) and in 47 out of 60 patients by omeprazole-amoxycillin-metronidazole (OAM) (78%; 95% CI 66-88%) (P = 0.22). Nine patients of each group available for follow-up reported adverse events (15.0 and 15.5%, respectively) without necessity of discontinuation of the study medications. Serious adverse events were not observed. CONCLUSIONS: Simple and convenient 1-week triple therapies consisting of omeprazole, amoxycillin and either clarithromycin or metronidazole are sufficiently effective in eradicating H. pylori infection.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8730252&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Cost of acid peptic disorders in a managed-care organization.

Segal R, Russell WL, Ben-Joseph R, Mansheim B.

University of Florida, College of Pharmacy, Gainsville, USA.

The purpose of this study was to determine the cost of managing ambulatory patients with symptoms of acid peptic disorders in a managed-care organization under actual clinical conditions. Study data were collected in a large independent practice association model health maintenance organization in Gainesville, Florida, from prescription records maintained in a computerized database and from patient medical records. Patients had to be started on a histamine2-receptor antagonist (H2RA) or the proton pump inhibitor omeprazole between 1992 and 1994. A total of 113 patients qualified for inclusion in the study; 57 received H2RAs, 27 received omeprazole, and 29 received combination therapy. The costs of procedures, physician visits, and drug therapy were considered in the economic evaluation. Costs were evaluated using two methods: the capitation total cost (CTC) and the fee-for-service total cost (FSTC). The mean CTC and FSTC for managing a patient with acid peptic symptoms for 6 months were $382 +/- 356 (range, $14 to $1820) and $456 +/- 368 (range, $52 to $1925), respectively. Drug costs represented 52% of the total FSTC and 62% of the total CTC. Drug costs were followed by the costs for encounters with primary care physicians, endoscopy, referral to specialists, and upper gastrointestinal (UGI) tract procedures. Documented outcomes were available for 85 patients. Compared with patients receiving H2RAs (n = 41), patients receiving omeprazole (n = 18) had significantly lower FSTCs ($317 +/- 219 compared with $423 +/- 307, respectively); diagnostic testing costs (for endoscopy, $0 compared with $44 +/- 119, respectively; for UGI procedures, $22 +/- 42 compared with $55 +/- 54, respectively); physician encounter costs ($66 +/- 40 compared with $86 +/- 38, respectively); and referral to specialist costs ($0 compared with $18 +/- 60, respectively). Patients receiving omeprazole also had more positive clinical outcomes than patients receiving H2RAs (78% compared with 49%, respectively), resulting in a more favorable cost of producing a successful outcome compared with patients receiving an H2RA. The cost of success was $407 for patients treated with omeprazole compared with $869 for patients treated with H2RAs. The findings of this analysis conducted under actual clinical conditions support findings of randomized clinical trials showing the cost-effectiveness of proton pump inhibitors.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8733992&dopt=Abstract omeprozole Prilosec